Thinned young apple powder prevents obesity-induced neuronal apoptosis via improving mitochondrial function of cerebral cortex in mice.

Mitochondrial dysfunction is one of the triggers for obesity-induced neuron apoptosis. Thinned young apple is getting more attention on account of the extensive biological activities because of rich polyphenols and polysaccharides. However, the neuroprotective effect of thinned young apple powder (YAP) is still unclear. The aim of the present study was to investigate the preventive effect of YAP on obesity-induced neuronal apoptosis. C57BL/6J male mice were divided into 5 groups, control (CON), high fat diet (HFD), HFD + orlistat (ORL), HFD + low-dose young apple powder (LYAP) and HFD + high-dose young apple powder (HYAP) groups and intervened for 12 weeks. It was found that the YAP effectively reduced body weight gain. Importantly, the levels of pro-apoptosis protein were lower in LYAP and HYAP groups than the HFD group, such as Bak/Bcl2 and cleaved caspase3/caspase3. Pathway analysis based on untargeted metabolomics suggested that YAP alleviated obesity-induced neuronal apoptosis by three main metabolic pathway including arginine metabolism, citrate cycle (TCA cycle) and glutathione metabolism. Meanwhile, YAP improved the protein expression of mitochondrial respiratory chain complex, maintained the homeostasis of TCA cycle intermediates, protected the balance of mitochondrial dynamics and alleviated lipid accumulation. In addition, the levels of several antioxidants in cerebral cortex were higher in HYAP group than the HFD group like superoxide dismutase (SOD) and catalase (CAT). In summary, YAP supplementation suppressed neuronal apoptosis in the cerebral cortex of HFD-induced obesity mice by improving mitochondrial function and inhibiting oxidative stress.